Program

In Bio-Inspire a technology platform will be developed for full tissue regeneration of a range of critical sized bone defects. The program consists of five integrated research tracks, or so called work packages. Recombinant peptide design of WP1 is incorporated in the WP2, WP3 and WP4 that are responsible for the therapeutic materials design. WP5, the orthopaedic studies, assures integration between the track from bio-mechanical an clinical-therapeutic point of view.
 

  • Work Package 1 : Collagen I based recombinant peptide scaffolds

    In work package 1 the following biomaterials will be developed, based on Fujifilm's recombinant Cellnest peptide:

    • Microspheres and scaffolds for bio-mimetic mineralisation (to be used in work package 2)
    • Mircospheres and in situ gelating system for growth factor delivery (to be used in work package 3) 
    • Cell carrier for delivery of stem cells (to be used in work package 4)
  • Work Package 2 : Biomimetic mineralisation

    The activity of WP2 focuses on the development of new superparamagnetic bone and osteochondral scaffolds by incorporation of defined amounts of iron ions in the structure of the mineral phase nucleated on the RCP matrix. The new scaffolds will have the ability to be remotely activated by external signal and to emit local magnetic field that can directly stimulate tissue regeneration. Besides this, the superparamagnetic mineral phase can be internalized by cells, thus providing a new appoach for guiding cells in advanced tissue engineering procedures. The new bio-devices wil be extensively characterized by chemical-physical, morphological and mechanical analyses, as well as by in vitro and in vivo tests.

    Objectives:

    • Transfer of the technology for the production of RCP scaffolds
    • Establishment of the procedures for scaffolds with graded mineralization
    • Completion of the scaffold development
    • Preclinical trials with the new bone scaffolds, the new osteochondral scaffolds, and the new superparamagnetic scaffolds
    • End evaluation of the new bio-devices
  • Work Package 3 : Growth factor release

    This work package is dedicated to the design of a delivery system for FDA-approved growth factors and new peptides derived from growth factors. This delivery system will be based on RCP microcarriers with the ultimate aim to induce bone formation.

    Objectives:

    1. Tuning the release profile of growth factor/peptides from collagen I based recombinant peptide microscarriers.
    2. Selection of new active peptides, growth factors or cytokines. Investigation of their effect on angiogenesis, attraction of MSC's and osteogeneic differentiation.
    3. Assess the effects of growth factor or peptide loaded microcarriers on bone formation.
  • Work package 4 : Cell therapy

    This work package is dedicated to the delivery of cells on micro-carriers to the bone defect area for neo-vascularization (EPC's) and bone regeneration (MSC's) purposes. The technique and culture conditions for MSC stem cell expansion play an important role for the maintenance of their differentiation potential, and for the genotoxic stress and ageing phenomena.

    Objectives:

    • Improvement of cell harvesting procedures of MSC's and EPC's from cell sources, including full cell characterization. Especially the harvesting of EPC's out of patients-based sources is point of investigation.
    • Controlled cell multiplication of primary cells to generate substantial amounts for therapeutic purposes, by use of new recombinant collagen I based recombinant peptide microcarriers.
    • Improved cell survival rates by minimal invasive injections of cells on new injectable micro-carriers
    • Combined use of EPC's and MSC's for adequate cellular cross-talks and synergistic therapeutic effects
  • Work Package 5 : Orthopaedic studies

    Aim of this work package is to access in vivo the functionality and regenerative capacity of biomimetic scaffolds, drug delivery carriers and cell-loaded microcarriers. Focus will ly on the presence of synergy between the different therapeutic approaches. The combination of a bio-mimetic scaffold implant with a growth factor releasing microcarrier, and the combination of a bio-mimetic scaffold with cell therapy will be evaluated in mainly large animal models. Implants will be evaluated by X-rays (at regular intervals), stereo-microscopy, histology, histomorphometry, SEM, and 3D micro-CT focus on synergistic effects.

    Deliverables are:
    1. New model for tissue regeneration
    2. Pre-clinical bio-mineral plus growth factor (GF)
    3. Integrated in-vivo studies (first round data available)
    4. Full data package of combined therapy (for move to clinic)

Partners

Bone Therapeutics SA

Erasmus Medical Center

Fraunhofer Institute

Fujifilm Manufacturing B.V.

Medicyte

ISTEC - CNR

University of Bologna

Marie Curie Actions

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The research leading to these results has received funding from the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement n° 607051.